The Two Kisspeptin Neuronal Populations Are Differentially Organized and Activated by Estradiol in Mice
The Two Kisspeptin Neuronal Populations Are Differentially Organized and Activated by Estradiol in Mice
复制标题
DOI：
10.1210/en.2013-1120
复制
发表时间：
2013-08-01
期刊：
影响因子：
4.8
通讯作者：
Bakker, Julie
中科院分区：
文献类型：
--
作者：
Brock, Olivier;Bakker, Julie
在啮齿类动物中，kisspeptin表达神经元位于下丘脑的2个脑核团（前腹侧室周核/室周核连续体[AVPv/PeN]和弓状核[ARC]），并受性类固醇调节。通过使用野生型（WT）和芳香酶敲除（ArKO）小鼠（不能将睾酮转化为雌二醇）和免疫组织化学，我们观察到WT雌性在出生后年龄（出生后第5天[P5]至P25）ARC中的kisspeptin肽表达持续增加，而WT雄性在P25之前没有显示任何表达。Kisspeptin肽的表达也存在于ArKO女性，但在出生后早期没有增加，这表明ARC中的Kisspeptin肽表达是由雌二醇依赖性和非依赖性机制组织的。我们还比较了成年雄性和雌性小鼠组之间的kisspeptin肽的表达，这些小鼠保留性腺完整或性腺切除，并用雌二醇（E-2）或DHT治疗或不治疗。在ARC中，kisspeptin肽的表达下降后性腺切除术，但完全获救的E-2或DHT治疗在每个性别/基因型。然而，与WT受试者相比，ArKO中的kisspeptin肽表达较低。在AVPv/PeN中，ArKO雌性显示出雄性典型的kisspeptin肽表达，并且成年E-2处理部分恢复了kisspeptin肽表达。最后，我们发现，在P5和P15之间或P15和P25之间，WT和ArKO小鼠经E-2处理后，AVPv/PeN kisspeptin肽的表达在P5时仍然是雄性化的，但从P15开始雌性化。总之，2 kisspeptin神经元群体（AVPv/PeN与ARC）似乎是差异组织和激活E-2。
In rodents, kisspeptin-expressing neurons are localized in 2 hypothalamic brain nuclei (anteroventral periventricular nucleus/periventricular nucleus continuum [AVPv/PeN] and arcuate nucleus [ARC]) and modulated by sex steroids. By using wild-type (WT) and aromatase knockout (ArKO) mice (which cannot convert testosterone into estradiol) and immunohistochemistry, we observed that WT females showed a continuous increase in kisspeptin peptide expression in the ARC across postnatal ages (postnatal day 5 [P5] to P25), whereas WT males did not show any expression before P25. Kisspeptin peptide expression was also present in ArKO females but did not increase over this early postnatal period, suggesting that kisspeptin peptide expression in the ARC is organized by estradiol-dependent and -independent mechanisms. We also compared kisspeptin peptide expression between groups of adult male and female mice that were left gonadally intact or gonadectomized and treated or not with estradiol (E-2) or DHT. In the ARC, kisspeptin peptide expression decreased after gonadectomy but was completely rescued by either E-2 or DHT treatment in each sex/genotype. However, kisspeptin peptide expression was lower in ArKO compared with WT subjects. In the AVPv/PeN, ArKO females showed a male-typical kisspeptin peptide expression, and adult E-2 treatment partially restored kisspeptin peptide expression. Finally, we showed that, after E-2 treatment of WT and ArKO mice between either P5 and P15 or P15 and P25, AVPv/PeN kisspeptin peptide expression could be still masculinized at P5, but was feminized from P15 onward. In conclusion, the 2 kisspeptin neuronal populations (AVPv/PeN vs ARC) seem to be differentially organized and activated by E-2.